It is proposed to test whether a series of cocarcinogen derivatives known to cause a graded biological response also have a graded effect upon structural or functional properties of cellular organelle membranes. We will continue our examination of the effects of cocarcinogens such as lipophilic phorbol esters upon membrane transport by plasma cell membranes. Attempts will be made to examine the nature of the effect of cocarcinogens on transport of phosphate and Ca ions, and also on levels of cyclic nucleotides. Specifically, the effect of phorbol-induced changes on cyclic AMP and cyclic GMP will be studied. Also, the observed phorbol-induced changes in phosphate transport will be further studied, and attempts made to learn whether changes in the transport of calcium ions are observed. One question of interest is whether previously observed increases in cyclic GMP levels or decreases in cyclic AMP levels are secondary to transient changes in Ca ions. Increases by tetradecanoyl phorbol acetate (TPA) in the Calcium-ATPase have been reported earlier. BIBLIOGRAPHIC REFERENCES: K. A. Jacobson, C. E. Wenner, G. Kemp, and D. Papahadjopoulos: Surface properties of phorbol esters and their interaction with lipid monolayers and bilayers. Cancer Res. 35: 2991-2995, 1975.